Atrial rate sensitive cardiac pacer circuit

ABSTRACT

An electrical pacer device which responds to cardiac demand so as to alter the cardiac output in a fashion to satisfy that demand. Changes in the fundamental period of the atrial electrical cycle are detected and averaged over a predetermined time interval and the resulting control signal is used to raise and lower the ventricular heart rate to increase and decrease the aforesaid cardiac output. At the same time, means are provided for continuously driving the ventricular rate toward a predetermined lower rate (the at rest rate) on a time cycle which is significantly longer than the above-mentioned predetermined time interval.

BACKGROUND OF THE INVENTION

I. Field of the Invention

This invention relates generally to cardiac pacer apparatus and morespecifically to an improved cardiac pacer system which is responsive tothe metabolic needs of the body and which optimizes cardiac output(blood flow) to suit those metabolic needs.

II. Discussion of the Prior Art

The human body can be viewed as a machine that is used by the mind toallow it to function in the physical world. It is started at conceptionand continues running until death, and like any machine, it requiresenergy to operate. The amount of energy required varies from "idle" whensleeping to "full throttle" during periods of maximum exertion and thisenergy is supplied through the blood stream. The heart, which is thepump for this system, must maintain this flow of energy so as to equalthat required by the body during any given condition, such as duringperiods of sleep or during exercise.

In a normal heart, cardiac demand controls the cardiac output (bloodflow rate) by virtue of the conduction of electrical impulses from theSA node to the AV node and from there down the bundle of His whichpasses to the ventricular septum, where it divides into two large bundlebranches which supply both ventricles. Each branch spreads along theendocardial surface of the septum to the apex of the heart and thenturns upward over the lateral wall of each ventrical. The Purkinjefibers of the AV bundle enter the ventricular walls and finally fusewith the heart muscle fibers and, in this way, each muscle fiberreceives the impulse. When conduction system failures occur, the AVtrigger signal arriving from the atrium is impacted and as a result,cardiac demand does not effectively control the cardiac output.

Prior art pacemakers attempt to replace the defective conduction systemby establishing an artificially fixed heart rate to control a pulsegenerator for stimulating the ventricles. The heart rate is setsufficiently high to supply enough cardiac output to allow bodymaintenance as well as enough reserve to allow useful work. So-calledP-synchronous prior art pacer systems attempt to use the AV trigger fromthe atrium to alter the heart rate so as to allow the cardiac output tobetter match cardiac demand. P-synchronous pacer devices have not beenaltogether successful in that the atrial electrical activity for acardiac system, while containing the information concerning cardiacdemand, is not a precise system and like most biological systems, it isvery difficult to measure atrial trigger signals with a high degree ofaccuracy and reliability. Most prior art pacemaker systems, such as theP-synchronous system, attempt to duplicate the very complex function ofthe cardiac electrical system. However, this tends to duplicate the verysame problems that the P-synchronous system is intended to correct,primarily because of improper and imperfect signal sensing, detecting,processing and controlling.

In accordance with the teachings of the present invention, the problemof defective conduction of atrial trigger signals to the ventrical isapproached from the standpoint of correcting the intent of the cardiacoutput and cardiac demand relationship instead of attempting toreproduce the rather complex control system within the heart itself. Inthat the atrial electrical activity contains the information concerningcardiac demand and since this information is directly related to theP-wave rate within this activity, in accordance with the presentinvention, the ventricular pacing rate is controlled as a function ofdetected changes of the P-wave rate.

SUMMARY OF THE INVENTION

In accordance with the present invention, a control circuit is providedfor a conventional demand, R-wave inhibited, ventricular pacer wherebythe pacer pulse rate of that device is controlled as a function ofchanges in the detected P-wave rate. A suitable lead having astimulating electrode adapted to abut the apex of the ventricle andhaving further sensing electrodes disposed proximally of the tip orstimulating electrode so as to be disposed near the upper right wall ofthe atrium for sensing P-wave activity is coupled to the electronicspackage. The signals picked up at the sensing electrodes, which mayinclude P-waves, R-waves, T-waves, muscle artifacts as well as noise,are applied to a P-wave detector which serves to filter and shape theincoming signals and to discriminate against all but the P-wave signals.Furthermore, since the cardiac system is not working properly, atrialflutter, premature atrial contractions (PAC's) and other anomalies ofthe atrium may be present. However, these anomalies, though not normal,still contain the information concerning the cardiac demand and the rateof these latter signals will vary according to that demand. The controlcircuit of the present invention extracts the change in the rate ofthese signals and uses this rate change to develop a control signal forthe conventional demand/inhibit pulse generator driving the heartthrough the ventricular stimulating pulses applied to the heart by wayof the stimulating tip electrode.

The signal applied to the demand/inhibit pacemaker to control theventricular stimulating rate in accordance with cardiac demand in amanner similar to normal physiological control must accomplish twothings.

(1) The actual ventricular stimulating rate must be raised and loweredby the cardiac demand signal, but must not go below the lowest allowablepacing rate and this rate must not be changed abruptly, but instead,over a physiologicallay compatible time, typically one to three minutesin the normal cardiac system.

(2) Any rise in the heart rate should be sufficiently long to sustainphysical activity until the activity is completed, but not allow thatactivity to continue past the point of serious fatigue. This time in thenormal cardiac system is approximately 20 to 40 minutes.

In the pacer control device of the present invention the firstcondition, that of raising and lowering the heart rate, is accomplishedby coupling the output from the P-wave detector circuit to a P-waveaveraging circuit in which small quantities of electrical charge, oneincrement for each detected P-wave, are summed in an integratingcapacitor which is arranged to lose its charge with a time constant ofapproximately 30 seconds, thus producing a voltage related to the numberof P-waves sensed and detected over the preceding approximately 1.5minutes of any given time. The averaging circuit is designed to have adynamic range from 0 P-waves per minute to approximately 250 P-waves perminute. In that the signal is sensed from electrodes which are"floating" in the atrium of the heart, it is possible that severalP-waves in a row may go undetected and then capture is again regained.To preclude this from occurring, the averaging circuit employed includesa threshold level that responds such that the effect of 0 to 50 P-wavesper minute is diminished.

The second of the conditions listed above, i.e., that of alwaysreturning the pulse generator pacing rate to the lowest allowable rate,is accomplished by using a differentiating network incorporating a timeconstant of approximately 10 minutes. This allows a change in the P-waveaveraged rate to be used to produce a corresponding change in theventricular rate, but will always try to return the pacing rate to thelowest allowable preset rate in a time interval of approximately 30minutes.

By using the system of the present invention in combination with aconventional R-wave inhibited demand pacemaker, the existing cardiacdemand effectively controls the cardiac output by detecting thefundamental period of the atrial electrical cycle and using the changesin this period averaged over a 1.5 minute time span to raise and lowerthe ventricular heart rate to increase and decrease the cardiac outputand in such a fashion that the control circuit strives to return theventricular rate to a pre-established resting rate over a 30 minute timecycle. The system of the present invention thus comprises a first ordercontrol system satisfying the fundamental requirements of a truephysiologically compatible pacemaker. The relationship of cardiac outputbeing equal to cardiac demand in the present system will satisfy thephysiological intent of the biological system of the body, provided aproper choice of circuit operating parameters are chosen.

OBJECTS

It is accordingly a principal object of the present invention to providea new and improved cardiac stimulating system.

Another object of the invention is to provide a cardiac stimulatingsystem in which cardiac output is made to track cardiac demand.

A still further object of the invention is to provide a control networkfor a conventional demand inhibited pulse generator whereby the rate atwhich pacer pulses are produced is determined by changes in atrialelectrical activity rather than by the atrial events (P-waveoccurrences) themselves.

A yet still further object of the invention is to provide a cardiacpacing system which closely emulates the physiological responses of theheart to changes in metabolic need.

A yet further object of the invention is to also provide means foradapting the stimulating rate of a cardiac pacer to the metabolicdemands of the body in patients where the normal conduction system ofthe heart is defective.

A still further object of the invention is to provide an electroniccircuit which may be simply adjusted on an adaptive basis to changes incardiac demand as reflected by changes in atrial electrical activity.

It is still a further object of the invention to provide a device ofvery simple construction, which is highly reliable and consumes verylittle electrical energy so that it may be implanted in the body of thepatient.

Other objects and advantages of the invention will appear from readingthe following description of the invention, with reference to theaccompanying drawings.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a general block diagram of the preferred embodiments;

FIG. 2 is a schematic electrical diagram of the controller circuits usedto control a conventional demand/inhibited pulse generator in accordancewith the present invention; and

FIG. 3 is a curve illustrating the transfer function of the controllernetwork of FIG. 2.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring first to FIG. 1, the general arrangement of the presentinvention will be set forth. Indicated by numeral 1 is a heart organwhich is divided into its four chambers by the dotted lines. The heart,of course, is a pump for circulating blood and the cardiac output isgenerally equal to the stroke volume of the heart multiplied by theheart rate. This cardiac output or flow is shown as being delivered tothe body identified by numeral 2. A first portion of the cardiac outputis needed to supply adequate nutrition of cells and to maintain theinternal environment of the body. Another portion of the cardiac outputis required by certain organs to perform work. These two componentscombine in the body's metabolic system indicated schematically bynumeral 3 and present chemical, electrical and possibly other inputs tothe atrium of the heart. Cells in the SA node initiate the electricalimpulse resulting in contraction. The impulse progresses as a wave overthe atria and reaching the AV node. From there, the wave progressesthrough the atrioventricular bundle to the ventricle. In patientssuffering from second or third degree heart block there is no longer aone-to-one relationship between atrial contractions and ventricularcontractions. The atria will continue to contract at the rateestablished by the nerve impulses, but the ventricles may adopt a slowerrate.

In the normal heart, all groups of muscle fibers in the atria and theventricles contract in almost simultaneous phase. This forces blood outof the atria and into the ventricles, followed by ventricularcontraction, which forces blood into the pulmonary artery and the aorta.In cases of atrial fibrillation, the muscle fibers of the atria contractalmost continuously and asynchronously. In consequence, the muscles ofthe atria undergo irregular twitchy movements. More importantly, thismeans that the AV node is stimulated in an irregular fashion so that theventricles contract normally, but with a completely irregular rhythm.

Even in patients suffering from second or third degree heart block andeven in instances where atrial fibrillation is in process, changes inthe body's metabolic need still reflect changes in the atrial electricalactivity. A sensing electrode on a lead disposed in the right antrium ofthe heart detects electrical signals, principally P-waves, and they arerouted through the lead to a P-wave detector circuit 4. The detectorcircuit may include a band-pass filter for discriminating againstelectrical artifacts, other than P-waves, and for thresholding andshaping the signals emanating from the band-pass filter. The resultingsignals are applied to an averaging circuit 5 which comprises anintegrator network driven by a pulse generator, whereby predeterminedmeasures of charge are stored in a capacitor associated with theintegrator circuit of the P-wave averager 5. A resistive discharge pathis also associated with that capacitor such that it tends to lose chargewith a time constant of approximately 30 seconds. As a result, theoutput from the averaging circuit 5 is a voltage which is related to thenumber of P-waves sensed over approximately the preceding three timeconstant intervals or, typically, 1.5 minutes. This signal is applied tothe ventricular rate restoration circuit 6 which, in the preferredembodiment, comprises a differentiating network which incorporates arelatively long time constant, typically 10 minutes. As such, thecircuit 6 allows a change in the P-wave averaged rate to be used toproduce a corresponding change in the ventricular rate, but it willalways operate in a direction to return the ventricular rate to thelowest allowable rate in approximately 30 minutes. The signal appearingon line 7 may then be a current which is proportional in amplitude tochanges in the P-wave rate. By applying this signal to a timing elementin a conventional R-wave inhibited demand pacemaker its normal pacingrate of that device is made to deviate from its preset lowest allowableheart rate. In the block diagram of FIG. 1, the demand pulse generatoris identified by numeral 8. It may, for example, comprise a Model 0503MINILITH^(TM) cardiac pacer manufactured by Cardiac Pacemakers, Inc. ofSt. Paul, Minnesota, the assignee of the instant patent application. Forthose desiring information on the details of construction and operationof that pulse generator, reference is made to the Anderson et al U.S.Pat. No. 4,041,953 which is assigned to the assignee of the instantapplication. The manner in which the control circuitry ties into thatdemand/inhibit cardiac pacer will be set forth in greater detailhereinbelow when the specifics of the construction of the overall systemare described.

The output pulses from the demand, R-wave inhibited pulse generator 8are applied through a lead to a further electrode disposed in theventricle of the heart. In practice, the atrial sensing electrodes andthe ventricular stimulating electrode may be disposed on a common leadsuch that only a single catheter need be routed through the vascularsystem and into the heart to obtain the sensed atrial signals, thesensed ventricular signals and to stimulate the ventricle.

With the foregoing organization and operating principles in mind,consideration will now be given to the details of the implementation ofthe preferred embodiment wherein the inventive aspects may be realizedin an actual working circuit.

Referring then to FIGS. 2a and 2b, there is shown a preferred embodimentof a circuit capable of sensing changes in physiological demand and forproducing a control signal which, when applied to a conventional demandpacemaker, will cause the pacing rate of the stimulating pulses appliedto the ventricle to change as a function of physiological demand. Shownenclosed by dashed line box 10 is a P-wave sensing circuit which isadapted to have its input terminals 12 and 14 coupled to electrodesdisposed proximate the high atrial wall of the patient so as to senseelectrical signals corresponding to P-wave activity in the atrium. Theelectrode terminal 12 labeled P SENSE+is coupled through a resistor 16to a junction 18 to which is connected a first terminal of a capacitor20, a capacitor 22 and a resistor 24. The remaining terminal of thecapacitor 20 is connected to circuit ground while the resistor 24 hasits other terminal coupled through a capacitor 26 to the inverting inputof an operational amplifier 28. The input terminal 14 labeled P SENSE-islikewise coupled through a resistor 30 to a junction point 32. The otherterminal of the capacitor 22 is coupled to this junction point as is afirst terminal of a further capacitor 34 and a resistor 36. The otherterminal of the capacitor 34 is connected to circuit ground and theremaining terminal of the resistor 36 is coupled through a capacitor 38to the non-inverting input of the operational amplifier 28. Thenon-inverting input of the operational amplifier 28 is also coupledthrough a further capacitor 40 to ground and a resistor 42 is coupled inparallel therewith. A predetermined bias is applied to the non-invertinginput by way of a resistor 44 which is adapted to be connected to asource of regulated voltage V₁.

The operational amplifier 28 has a feedback circuit including a parallelcombination of a capacitor 46 and a resistor 48 connected between itsoutput junction 50 and the inverting input of the amplifier. Thecomponent values of the resistors and capacitors thus far identified areselected so as to cause the operational amplifier 28 to function as aband-pass filter whose center frequency corresponds to the predominantfrequencies of received P-wave signals, yet providing relatively highattenuation of frequency components above and below that centerfrequency.

The output from the band-pass filter appearing at the junction 50 isconnected as a first input to a set of comparators indicated generallyby numerals 52 and 54. As can be seen from the drawing, the comparator52 comprises an operational amplifier 56 having its inverting inputconnected by conductors to the junction 50. A regulated voltage V₁ isconnected to a first side of a bias resistor 58 whose other side isconnected to a junction tied directly to the non-inverting input of theoperational amplifier 56. A resistor 60 is connected directly across theinputs to the operational amplifier 56 and a capacitor 62 is coupledbetween the non-inverting input thereof and circuit ground. Withreference to the comparator 54, it too includes an operational amplifier64 whose non-inverting input is connected directly to the junction point50 at the output of the band-pass filter operational amplifier 28. Theinverting input of the operational amplifier 64 is coupled to circuitground via a parallel combination of a capacitor 66 and a resistor 68. Afurther resistor 70 is coupled directly across the input terminals ofthe operational amplifier 64.

The output from the operational amplifier 56 is coupled through atransistor 72 which is connected as a diode to a junction point 74.Similarly, the output from the operational amplifier 64 of thecomparator 54 is coupled through a diode connected transistor 76 to thesame junction point 74. Thus, the junction point 74 comprises aso-called "dot OR" of the respective outputs from the comparators 52 and54. Thus, P-waves of either positive or negative polarity passingthrough the band-pass filter network and of an amplitude exceeding thethreshold defined for the comparators 52 and 54 will cause an outputpulse to appear at the junction point 74.

To preclude paced ventricular stimulating pulses which may feed backthrough the heart from adversely affecting the desired operation of therate sensitive controller, an inhibiting circuit including thetransistors 75 and 77 is included. The base of transistor 75 is adaptedto be coupled through a resistor 79 to the conventional demand/inhibitpacer with which the controller hereof is adapted to be used.Specifically, and with reference to FIG. 6 of the aforereferencedAnderson et al U.S. Pat. No. 4,041,953, the refractory signal to beapplied to the base of the transistor 75 may be obtained at thecollector electrode of the transistor labeled Q103 in that figure. Theemitter of NPN transistor 75 is tied to circuit ground and its collectoris coupled through a resistor 81 to the base electrode of the transistor77. A capacitor 83 is connected in parallel with thecollector-to-emitter path of the transistor 75. A bias resistor 85 isconnected between the voltage source V₁ and the base electrode of thetransistor 77. The collector electrode of this last-mentioned transistoris connected by a conductor 87 to the output of the P-wave sensingcircuit 10.

The portion of the circuit shown enclosed by dashed line box 76a may beconsidered as a frequency to voltage converter and includes as itsoperational elements a one-shot circuit indicated generally by numeral78 and an integrator circuit indicated generally by numeral 80.Specifically, the dot OR junction 74 of the P-wave detecting circuit 10is coupled through a resistor 82 to the base electrode of a PNPtransistor 84. The collector electrode is connected to the rail 86 ofthe one-shot circuit which, in turn, is directly connected to theregulated voltage source V₁. A bias resistor 88 is connected between thesource V₁ and the base electrode of the transistor 84. A pair ofcross-coupled transistors 90 and 92 have their respective emitterelectrodes connected to the rail 86 and the collector electrode of thetransistor 90 is connected directly to the collector electrode of thetransistor 84 at a junction 94. The collector electrode of thetransistor 90 is coupled through a timing capacitor 96 to the baseelectrode of the transistor 92. The collector electrode of thetransistor 92 is tied directly to the base electrode of the transistor90. A resistor 98 connects between the aforementioned junction point 94and circuit ground. Likewise, a resistor 100 is connected between thebase electrode of the transistor 92 and circuit ground. A furtherresistor 102 connects the common junction between the base electrode ofthe transistor 90 and the collector electrode of the transistor 92 tocircuit ground.

The output from the one-shot circuit is coupled through a resistor 104to the base electrode of a NPN transistor 106 forming a part of theintegrating circuit 80. The integrating capacitor 108 is coupled betweenthe base electrode of the transistor 106 and circuit ground. The emitterelectrode of the transistor 106 is coupled through a resistor 110 toground and its collector electrode is tied to the voltage source V₁.Bias is provided to the transistor 106 by way of a voltage dividerincluding the resistors 112, 114 and 116. Specifically, the resistor 112is connected at one side to the voltage source V₁ and its remainingterminal is tied in common with a first terminal of the resistors 114and 116. The remaining terminal of the resistor 114 is connected to thebase electrode of the transistor 106 while the remaining terminal of theresistor 116 is connected to circuit ground.

Shown enclosed by the dashed line box 118 is a current source controllercircuit. As is illustrated, the output from the frequency to voltageconverter circuit 76a appearing on line 120 which connects to theemitter electrode of the transistor 106 is coupled through adifferentiating capacitor 122 to the non-inverting input of anoperational amplifier 124. Also connected to this input is a voltagedivider including series connected resistors 126 and 128 which arecoupled between the regulated voltage source V₁ and circuit ground. Thecommon junction between the resistors 126 and 128 is coupled through afurther resistor 130 to the noninverting input of the operationalamplifier 124.

A further reference voltage V₂ is coupled to the inverting input of theoperational amplifier 124 by way of a resistor 132. A NPN transistor 134is employed as a feedback element for the operational amplifier and, inthis regard, has its base electrode coupled to the output terminal 136of the operational amplifier 124 and its emitter electrode tied to theinverting input of that amplifier.

With continued reference to the current source controller circuit 118,the output terminal 136 of the operational amplifier 124 is alsoconnected to the base electrode of a PNP transistor 138 and the emitterelectrode of that transistor is connected to a common point between twoseries connected resistors 140 and 142. The remaining terminal of theresistor 140 is connected to the voltage source V₁ whereas the remainingterminal of the resistor 142 is arranged to be connected to the voltagesource V₂. The collector electrode of the transistor 138 is coupled viaconductor 144 to the non-inverting input of the operational amplifier124.

The current source itself is shown enclosed by the dashed line box 146and is adapted to be coupled to the current source controller 118 by wayof a bistable magnetic reed switch 148. When a permanent magnet isbrought into proximity of the switch 148 with its north pole properlyoriented, the switch arm 150 will be brought into contact with thecontact 152 and it will remain in this position once the permanentmagnet is again removed. To switch the magnetic reed switch 148 to itsopposite state, the polarity of the magnet is reversed as it is broughtinto proximity of the magnetic reed switch causing the switch arm 150 tomove into contact with the contact 154. Again, when the permanent magnetis removed from a position in proximity to the reed switch, the switcharm 150 will remain in contact with the contact 154.

When the switch arm 150 abuts the contact 152, the system is said to beoperating in its atrial rate sensitive mode. When the magnetic reedswitch is operated such that its switch arm 150 contacts the contact154, the system will be operating as a conventional ventricular demandpacemaker.

Assuming that the magnetic reed switch has been operated to its atrialrate sensitive mode position, the collector electrode of the transistor134 will be connected to a junction point 156 in the current sourcecircuit 146. The current source circuit includes a pair of PNPtransistors 158 and 160 each having its collector electrode tied to thecommon junction point 156 and its emitter electrode tied to the rail 162which, in turn, is connected to the voltage source V₁. A further PNPtransistor 164 has its emitter tied to the rail 162 and its baseelectrode tied to a common junction 166 between the base electrode oftransistor 160 and the junction point 156. The collector electrode ofthe transistor 164 is coupled through a resistor 168 to a terminal 170which is adapted to be connected to a point in the constant currentcircuit of the demand cardiac pacer providing current to the pulsegenerator's timing capacitor. Typically, the terminal 170 may beconnected to the common point between the collector electrode oftransistor Q101 and the emitter electrode of transistor Q102 in thepacer circuit illustrated in FIG. 6a of the Anderson et al U.S. Pat. No.4,041,953.

Bias voltage is applied to the base electrode of the transistor 158 byway of a resistor 172 which is coupled between the rail 162 and the baseelectrode of the transistor 158. A further resistor 174 is coupledbetween the base electrode of the transistor 158 and the collectorelectrode of a NPN transistor 176. The emitter electorde of thislast-mentioned transistor is connected directly to circuit ground andits base electrode is coupled through a resistor 178 to the positiverail 162.

When the magnetic reed switch 148 is in its other position with theswitch arm 150 abutting the contact 154, the connection between theoutput of the current source controller 118 and the current source 146is broken and, instead, a resistor 180 is connected between the voltagesource V₂ and the aforementioned junction point 156.

OPERATION--FIG. 2

As was already indicated, the input terminals 12 and 14 are adapted tobe connected to sensing electrodes disposed in the upper right atrium ofthe heart. Typically, electrical activity applied to these terminalswill include P-waves, R-waves, T-waves, signals relating to muscleartifact and possibly other noise picked up by the sensing electrodes.These signals are brought into the P-wave filter and detector 10 whichincludes a band-pass filter comprising the operational amplifier 28 andits associated input and feedback resistors and coupling capacitors.Component values are chosen so that the band-pass filter will respondprimarily to P-waves and will attenuate other signals. The operationalamplifier 28 is selected so as to exhibit relatively high common moderejection, typically 30 db or more of the midband signals. The circuitcomponents are chosen so that the band-pass filter will have a centerfrequency of approximately 20 Hz with upper and lower cut-off points atapproximately 40 Hz and 10 Hz, respectively. The capacitors 20, 22 and34 provide the desired high frequency rejection and tend to eliminatefrequency components above around 100 Hz. The low frequency rejection ofthe band-pass filter is controlled primarily by capacitors 26 and 38while capacitors 46 and 40 primarily control the low passcharacteristics of the filter.

The operational amplifier 28 is arranged to provide a gain ofapproximately 100, the gain being determined primarily by the ratio ofthe value of resistor 48 to the sum of the values of resistors 16 and24. This relationship holds true in that the component values associatedwith the non-inverting input to the operational amplifier 28 are matchedto those associated with the inverting input of that amplifier.

The output from the band-pass filter appearing at junction 50 is appliedto the input of threshold comparators 52 and 54 by way of a couplingcapacitor 55. In that the signal is applied directly to thenon-inverting input of the amplifier 64 and to the inverting input ofamplifier 56 in the manner indicated, the battery voltage V₁ is appliedacross the voltage divider network including resistors 58 and 60 andresistors 70 and 68. This establishes the DC level or threshold for thecomparators. The incoming signal from the operational amplifier 28 whenno input signal is being impressed upon the terminals 12 and 14, resultsin the comparator amplifiers 56 and 64 producing an output signal thatis "high", i.e., near the power supply level. If a received P-wave ispositive, amplifier 56 will produce a low output while the output ofamplifier 64 will remain in the high state. However, if the input P-wavesignal exhibits a negative excursion, then the reverse would be true.Specifically, a negative going signal exceeding the thresholdestablished will cause the comparator 64 to output a low output whilethe output of amplifier 56 will remain in the high state.

The transistors 72 and 76 are connected as diodes and because of themanner in which their bases are tied together at the common junction 74,an OR logic function results. The use of transistors 72 and 76 insteadof conventional diodes provide a lower forward voltage drop whenconducting than would otherwise be obtainable. Appearing at the junction74, then, will be low going pulses or spikes corresponding to sensedsignals in the atrium which are of the proper frequency to pass throughthe band-pass filter and of an amplitude sufficient to satisfy thecriteria established for the comparators 52 and 54. These spikes arecoupled through the resistor 82 to the base electrode of the transistor84. Upon the occurrence of each spike, that base electrode is drivenlow, momentarily causing the transistor 84 to conduct such that itscollector goes high to trigger the one-shot circuit comprised of thecross-coupled transistors 90 and 92. This drives the one-shot to itsmetastable state where it remains for a period determined primarily bythe RC time constant determined by the resistor 100 and the capacitor96. In the preferred embodiment, this time period is set to be 150milliseconds and is a square wave of a predetermined amplitude. The 150millisecond pulse width is not critical.

At this point, it is appropriate to describe the operation of theinhibiting circuit comprised of the transistors 75 and 77. The terminal73 is arranged to be coupled to the demand, R-wave inhibited pacer at apoint at which the refractory signal of that device goes positive at theonset of the generation of a pacer pulse or when a naturally occurringR-wave signal is sensed by that pacer. The onset of the refractory pulsecauses the transistor 75 to become conductive and the current flowthrough the resistors 85 and 81 from the source V₁ causes a negativesignal to be applied to the base of transistor 77 turning it on. Oncetransistor 77 is conductive, the output from the P-wave filter/detectornetwork 10 is held high preventing the output from the network 10 fromtriggering the one-shot circuit 78. The time period that the conductor87 carries its high signal is determined by the component values of theresistors 81 and 85, the capacitor 83 and transistor 77. By setting thisto approximately 80 milliseconds, it has the capability of precludingnatural or paced R-waves or PVC's from firing the one-shot circuit. Theinhibiting circuit just described, then, is effective to precludeR-waves (paced or natural) as well as certain other artifacts fromaffecting the operation of the averaging circuit including the one-shotcircuit 78 and the integrator network 80 which it drives. The P-waveaverager 76a will be precluded from receiving paced R-waves and sensedR-waves that occur simultaneously in both the ventricle and the atrium.However, if there is a delay greater than 80 milliseconds as establishedby the sum of resistors 81 and 85 and the capacitor 83, the one-shotcircuit 78 will be tirggered. This leaves the P-waves as the predominantevent for triggering the one-shot 78.

Upon each triggering of the one-shot, the integrating capacitor 108 willbe fed an increment of charge determined by the width and amplitude ofthe output pulse from the one-shot circuit and the magnitude of thecoupling resistor 104. The resistors 112, 114 and 116 effectivelyestablish a DC voltage quiescent level upon which the output from theone-shot circuit rides. It is to be further noted that there is anadditional discharge path for the integratng capacitor 108.Specifically, it consists of the resistors 104 and 98 back in theone-shot circuit 78. Hence, if no energy at all is being transmittedinto this capacitor 108, i.e., the one-shot remains at its base leveland no P-waves are being detected, the voltage at the base of transistor106 will be set by the voltage derived from the source V₁ which is fedthrough the resistors 112, 114 and 116.

For each P-wave that causes the one-shot circuit to be triggered, itwill result in a small quantity of charge being dumped into theintegrating capacitor 108. Assuming for the moment that only a singlepulse from the one-shot 78 occurs during a long time interval, thecapacitor 108 will discharge through the path including resistors 104and 98 as well as through the path including resistors 114 and 116.These resistors are selected such that the time constant will beapproximately 30 seconds. Given an increase in voltage on the capacitor108 due to the triggering of the one-shot, that voltage will increasebut it will then decrease. At the end of approximately three timeconstants, i.e., typically about 11/2 minutes, the capacitor voltagewill have decayed back to its quiescent level. However, if the number ofP-waves sensed increases from 0 to some greater number, the voltage onthe integrating capacitor 108 will build up in steps in that chargesbeing added to it at a rate greater than what is being removed from it.Thus, the voltage on the capacitor is related to the rate at whichP-waves are received. The circuit is designed such that when the P-waverate reaches approximately 250 bpm, the voltage on the capacitor willcease to increase. With reference to FIG. 3, then, the dynamic range ofthe system can be represented graphically as indicated. It is importantto a clear understanding of the operation of the present invention thatit be realized that the system of the present invention is sensitive tochanges in P-wave rates and not merely to the occurrence of the P-waveitself as is the case with certain prior art pacers of the P-synchronoustype.

Referring to FIG. 3, if the detected P-wave rate is approximately 70 bpmand because of a physiologically induced change, the P-wave rateincreases or decreases, say, 5 bpm, then the voltage across thecapacitor 108 will vary slightly above and below the value existing atthe 70 bpm value. Likewise, if the atrial rate is running at 200 bpm andagain due to a change in physiologic demand there is an incrementalincrease of 5 bpm, the voltage change across the capacitor 108 will beabout the same as it was for a 5 bpm change centered around the 70 bpmlevel.

Furthermore, it is to be recognized that with a typical lead havingatrial sensing capabilities, the lead is free, within limits, to moveabout within the atrium. As such, it may sometimes be in direct contactwith the heart and other times it will not be. This results in thepossibility for massive fluctuations of the signal levels. It is thuspossible to get jumps from, say, 0 bpm being detected to around 70 bpmjust by virtue of lead movement. By providing a less sensitive zone onthe transfer characteristic from 0 to 50 bpm, changes due to leaddisplacement are effectively minimized.

After the control voltage which is proportional to the sensed P-waverate is developed at the emitter electrode of the transistor 106, it isfurther processed by the current controller circuit 118 in such afashion that only changes in the P-wave rate are of significance. Thechanges in atrial rate, of course, are dependent upon physiologic demandof the body.

The capacitor 122 in combination with the remainder of the circuitprovides a very large time constant, the capacitor acting as adifferentiator. Stated otherwise, it comprises a high pass filter withan extremely long time constant. The time constant is determined by thevalue of the capacitor 122 in microfarads multiplied by the effectiveresistance of resistors 126, 128 and 130 measured in megohms. This timeconstant may be set to be approximately in the range of from 5 to 35minutes, 10 minutes being typical. Under steady state conditions, thevoltage appearing at the positive input of the amplifier 124 will bedetermined by the magnitude of the DC voltage V₁ applied through theresistor network including resistors 126, 128 and 130. The capacitor 122will allow only changes in the integrated voltage to pass. These highfrequency components consist of any changes that are observed in thecontrol voltage developed at the emitter of transistor 106. With thetime constant chosen, upon the occurrence of a sudden change in theinput, approximately 30 minutes, i.e., approximately three timeconstants, are required for the control voltage to return to itsquiescent or steady state level. This 30 minute period corresponds quiteclosely to that which matches human physiological requirements. That isto say, following significant exercise, approximately 20 to 30 minutesare required for the heart rate to return to the at rest rate.

It is to be noted, then, that the averager circuit 76 provides a timeconstant in the range of from 15 to 45 seconds, about 30 seconds beingpreferred in that it yields approximately a 11/2 minute windowcorresponding to normal physiologic increases of the cardiac rate. Asmentioned, the differentiator, including the large capacitor 122, mayhave a time constant of approximately 10 minutes, defining a 30 minutewindow, in which the control voltage returns to its quiescent levelfollowing the change which it experienced.

The control signal which is developed at the non-inverting input of theamplifier 124 is the actual control signal which is, at this point, afunction of the changes in P-wave rate, not the absolute value of theP-wave rate. The amplifier 124 is designed to convert that controlsignal into a current which may be injected into a conventional R-waveinhibited demand pacer in such a fashion that the rate at whichventricular stimulating pulses are generated will be adjusted as afunction of that control signal. Referring momentarily to FIG. 6a of theAnderson et al U.S. Pat. No. 4,041,953, the transistors Q101 and Q102,along with the resistors R103 and R104, comprise a constant currentgenerator. That current source sets up a voltage, then, that allows acurrent through transistor Q103 for charging up the pulse generator'stiming capacitor C101. That last-mentioned capacitor forms a portion ofthe RC time constant of the oscillator portion of the pacer pulsegenerator. By injecting current at the point indicated, the chargingtime of the capacitor C101 is decreased and the ventricular stimulatingpulses appearing across the Heart+ and the Heart- terminals willincrease, assuming that naturally occurring R-waves do not inhibit theoperation of that demand pacer.

When it is desired to use the physiologic demand control circuit ofFIGS. 2a and 2b with a conventional, commercially available ventricularR-wave inhibited demand pacer, it may be desirable to provide a meanswhereby the physiologic control may be selectively disengaged to therebyallow the demand pacer pulse generator to operate in its normal fashion.To accomplish this end, a magnetic reed switch 148 of the bipolar typeis provided. If a permanent magnet is brought into proximity of such adevice with the magnet aligned in a first direction, the switch arm 150can be made to abut a first one of the contacts 152 and 154. When themagnet is then taken away, the switch arm will remain in thisorientation. However, when the permanent magnet is reversed so that itsnorth pole is oriented in an opposite direction than before and againbrought into proximity with the magnetic reed switch, it will revert toits opposite state and remain there when the permanent magnet is againremoved. When the switch arm 150 abuts the contact 152, the system is inits so-called "rate-sensitive" or physiologic mode. However, when theswitch arm 150 is made to abut the contact 154 the circuitry of FIGS. 2aand 2b is effectively removed from its cooperating relationship with theR-wave inhibited demand pacer circuit although it continues to processatrial electrical signals in the manner described.

Amplifier 124 is a standard operational amplifier with a gain controlrange that is established by a resistor 132 and the voltage source V₂.This voltage source causes a current to flow through the resistor 132and away from the inverting input of the amplifier 124. This current isestablished by the difference of potential between V₂ and the voltageappearing at the inverting input of the amplifier. In accordance withstandard operational amplifier theory, because of the assumed infiniteinput impedance existing between the operational amplifier's two inputs,the voltage at the inverting input must be exactly equal to that at thenon-inverting input. Thus, the voltage at the non-inverting input is arepresentation of the detected and processed P-wave rate change. Theamplifier 124 then sets up a current through the transistor 134 which iscoupled back to the inverting input. As a result, the output from theoperational amplifier 124 establishes a current through the base-emitterjunction of transistor 134 causing the voltages at the inverting andnon-inverting inputs to be equal to each other. The operationalamplifier 124 then functions to establish a current through thetransistor 134 to ensure that that relationship holds true. In that thetransistor 134 is chosen to have a very high gain, its collector currentis effectively equal to the base-emitter current which it carries. Thecollector current, then, flows through the closed magnetic reed switchto the bases of the transistors 160 and 164. The collector current oftransistor 160 is thus equal to the current flowing through the emitterof transistor 134. As transistors 160 and 164 are matched, it can beseen that the current flowing out of the collector of the transistor 164must be equal to the current flowing through the resistor 132 to thereference source V₂ and is therefore proportional to the controlvoltage. It is this collector current which flows through the resistor168 which is injected into the point previously indicated on the R-waveinhibited demand pacer.

The resistor 168 in the collector circuit of transistor 164 provides asafety feature. It is chosen such that the maximum current which can beinjected will not cause the ventricular pacer stimulating pulses to begenerated at a rate greater than a predetermined maximum, e.g., 130 bpm.

A commercially available pacer pulse generator with which thephysiologic controller of the present invention may be used includes aso-called "mag rate" feature for determining battery status. Again, bybringing a permanent magnet close to the implanted pacer, a magneticreed switch is closed, causing the pacer to revert to its asynchronousmode wherein the frequency of the output pulses provides a measure ofthe state of depletion of the battery power source. This feature is moreparticularly explained in the Anderson et al Patent cited. In order tostill obtain that type of operation, a connection is established vialine 171 to the "mag rate" terminal depicted in FIG. 6a of the Andersonet al Patent. When the pacer is placed in its mag rate, the base of thetransistor 176 is no longer grounded causing transistor 176 to conductwhich, in turn, turns on the transistor 158. With this latter transistorconducting, the current mirror transistors 160 and 164 are turned offand no control current can be injected into the timing capacitor of theventricular pulse generator's oscillator. It is to be noted, however,that the turning off of the control current delivered to the pacer'soscillator does not inhibit the controller of FIG. 2 from continuing tomonitor atrial electrical activity and developing the appropriatecontrol signal proportional in amplitude to changes in the P-wave rate.As soon as the permanent magnet governing the mag rate operation isremoved, the current supply to the pacer's timing capacitor will berestored.

When the bipolar magnetic reed switch 148 is operated to cause theswitch arm 150 to abut the contact 154, the demand inhibited pacer willoperate in its conventional fashion without being controlled on thebasis of atrial activity. That is to say, the current line leading fromthe collector of the transistor 134 to the current mirror comprised ofthe transistors 160 and 164 is opened. A current passes to the source V₂through the current limiting resistor 180 and through the magnetic reedswitch to the current mirror such that a fixed or steady current isinjected into the R-wave inhibited pacer. By providing this steadyinjected current, desired pacing rate is provided. That is to say, whenoperating in its physiological mode, the basic lowest pacing rate whichthe pacer is allowed to produce is arranged to be somewhat lower thanwhat would normally be established when the system is functioningstrictly as a demand/inhibit pacer. Hence, if a patient is asleep, hispacer can slow down to, say, 60 bpm and reliance is placed upon thephysiologic demand to increase the pacer rate from that lowermost value.However, when the system is operating in strictly the R-wave inhibitedpacer mode, it is typical that its pacing rate be somewhere around 75bpm. By drawing a small, fixed quantity of current to the voltage sourceV₂ through the current limiting resistor 180 and through the magneticreed switch to the current mirror transistors 160 and 164 and from therethrough the resistor 168 to the timing capacitor of the demand/inhibitpacer, it raises the base pulse rate from the lower value to a slightlyhigher value corresponding to normal R-wave pacer operation.

With continued reference to FIG. 2b, the transistor 138 and itsassociated bias resistors 140 and 142 act as a voltage clamp for theoperational amplifier 124. The purpose of providing this clamp will nowbe explained. Normally, whenever a rapid rate change is detected, itoperates to raise or lower the ventricular stimulating ratecorrespondingly. However, if the system happens to be operating at afairly nominal ventricular rate, for example 80 bpm, and suddenlycapture is lost and the change in the P-wave rate drops drastically, thepacer will ultimately return to its lower rate limit. Since thedifferentiator responds to changes in either direction, this loss ofsensing would reduce the ventricular paced rate to the established lowerrate limit. Indeed, the control voltage on the non-inverting amplifierinput could be driven below the bias point set by reference voltage V₂.Since the feedback element in the inverting loop of the operationalamplifier 124 is an NPN transistor, i.e., transistor 134, this statecuts off the injected current to the R-wave inhibited pacer pulsegenerator and turns on clamping transistor 138 which then supplies thenecessary current needed to restore the non-inverting input to thereference set by V₂. The effect of this action is to produce ahysteresis characteristic to the long time constant created by thedifferentiator comprised of capacitor 122, resistors 126, 128 and 130.This hysteresis is based on the direction and magnitude of the atrialactivity rate change. The non-inverting input of the operationalamplifier 124 is also biased by resistors 126, 128 and 130 such that inthe quiescent state, the control signal, based on the change in theatrial activity, is zero. The clamp transistor 138 is turned onslightly, thus ensuring that transistor 134 is turned off and the pacerpulse generator is in its base rate.

An absolute limit on the amount of current which may be injected intothe timing capacitor in the R-wave inhibited pacer is set by resistor168. As more current is delivered to the pacer through this resistor,the voltage drop across this resistor increases to a point where thecollector current of transistor 164 no longer mirrors a collectorcurrent of transistor 160, but rather is limited to a maximum level thatcorresponds to the specified upper rate limit of the paced ventricularfrequency, typically 135 bpm.

The following table sets forth typical component values which may beused in implementing the present invention. It is to be understood,however, that the values indicated are illustrative and not limitative.

                  TABLE I                                                         ______________________________________                                        Component(s)                                                                  Resistors           Value (s)                                                 ______________________________________                                        16, 24, 30, 36      47        K                                               42, 44              24        M                                               48, 114             12        M                                               49, 137, 174        22        M                                               58, 68              10        M                                               60, 70              220       K                                               71, 73a, 85, 100, 102, 104                                                                        20        M                                               79, 132             1         M                                               81                  5         M                                               82, 98, 110, 142    2         M                                               88, 172, 178        30        M                                               112                 13        M                                               116                 7.5       M                                               126                 25        M                                               128                 14        M                                               130                 7.9       M                                               140                 5.1       M                                               168                 7.1       M                                               180                 18        M                                               Capacitors                                                                    20, 34              0.0015    microfarads                                     26, 38              0.15      microfarads                                     40, 36              220       picofarads                                      62, 66              .068      microfarads                                     83, 96              .01       microfarads                                     108                 3.3       microfarads                                     122                 33        microfarads                                     Transistors                                                                   72, 75, 76, 106, 134, 176                                                                         2N2484                                                    77, 84, 90, 92, 138, 158, 160, 164                                                                2N3799                                                    Op. Amps                                                                      28, 56, 64, 124     Type 4250                                                 ______________________________________                                    

The invention has been described herein in considerable detail, in orderto comply with the Patent Statutes and to provide those skilled in theart with information needed to apply the novel principles, and toconstruct and use such specialized components as are required. However,it is to be understood that the invention can be carried out byspecifically different equipment and devices, and that variousmodifications, both as to equipment details and operating procedures canbe effected without departing from the scope of the invention itself.

What is claimed is:
 1. Cardiac stimulating apparatus having means foradjusting the frequency of stimulation as a function of physiologicdemand, comprising in combination:(a) a pulse generator having timingmeans therein for determining the frequency at which cardiac stimulatingpulses are produced; (b) detector means for detecting natural atrialelectrical activity characteristic of physiologic demand and producingtrigger signals predominantly related to P-wave occurrences; (c) firstmeans/a monostable multivibrator/coupled to said detector means forproducing an electrical signal of predetermined energy content uponreceipt of each of said trigger signals; (d) second/integrator/meanshaving a first time constant coupled to receive said electrical signalsof predetermined energy content for producing a voltage proportional inamplitude to the average repetition rate of said P-wave occurrencesduring a predetermined time interval; (e) third means/a differentiatorcircuit/coupled to receive said voltage from saidsecond/integrator/means and having a second time constant which isrelatively long compared to said first time constant for producing acontrol signal proportional in amplitude to changes in the repetitionrate of said P-wave; and (f) fourth means for applying said controlsignal to said timing means in said pulse generator for changing thefrequency at which cardiac stimulating pulses are produced in accordancewith physiologic demand.
 2. The cardiac stimulating apparatus as inclaim 1 wherein said detector means comprises:(a) band-pass filter meanscoupled to receive said natural atrial electrical activity and having acenter frequency corresponding to the predominant frequency componentscomprising cardiac P-waves; and (b) comparator means coupled to theoutput of said band-pass filter means for producing said trigger signalswhen the amplitude of the output from said band-pass filter exceeds apredetermined threshold.
 3. Apparatus as in claim 1 and furtherincluding:(a) means coupling said pulse generator to said first meansfor inhibiting trigger signals from operating said first means for agiven time following the generation of a stimulating pulse by said pulsegenerator.
 4. Apparatus as in claim 3 wherein said first time constantis in the range of from 20 to 60 seconds and said second time constantis in the range of from 5 to 15 minutes.
 5. Apparatus as in claim 1wherein said fourth means comprises:(a) current source means adapted tobe coupled to said timing means in said pulse generator; and (b) currentsource controller means coupled to receive said control signal andadapted to be connected to said current source means for causing saidcurrent source means to produce a current of an amplitude proportionalto said control signal.
 6. Apparatus as in claim 5 and further includinga switch disposed between the output of said current source controllerand said current source for selectively permitting said control signalto affect said timing means.
 7. Apparatus as in claim 6 wherein saidswitch is a magnetically actuated bipolar switch.
 8. Apparatus as inclaim 5 wherein said current source controller means further includescurrent clamping means for restoring said current source controllermeans to a predetermined reference state following a sudden change insaid control signal.
 9. Apparatus as in claim 1 wherein said pulsegenerator comprises an R-wave inhibited demand type cardiac pacer havinga resistance-capacitance timing means and wherein said means forapplying said control signal to said timing means comprises means forinjecting current into said resistance-capacitance timing means. 10.Apparatus as in claim 1 wherein said first means comprises a monostablemultivibrator means.
 11. Apparatus as in claim 10 wherein said secondmeans comprises integrator means.
 12. Apparatus as in claim 11 whereinsaid third means comprises a differentiator circuit means.